Distinct developmental pathways from blood monocytes generate human lung macrophage diversity

<b>RNA-sequencing data sets</b>(1) Single-cell RNA-sequencing data of human lung myeloid cells from
MISTRG mice on day 21 post-transplantation with human CD34⁺ cells

(2) Single-cell RNA-sequencing data of human lung myeloid cells from
MISTRG mice on day 36 post-transplantation with human CD34⁺ cells

(3)
Bulk RNA-sequencing data of human intravascular monocytes, intravascular
macrophages, and extravascular macrophages from the lungs of MISTRG mice
engrafted with human CD34⁺ cells<br><b>Data collection methods</b>See Resource DOI<br><br><b>Publication abstract</b>The study of human macrophages and their ontogeny is an important
unresolved issue. Here, we use a humanized mouse model expressing human
cytokines to dissect the development of lung macrophages from human
hematopoiesis in vivo. Human CD34+ hematopoietic stem and progenitor cells
(HSPCs) generated three macrophage populations, occupying separate anatomical
niches in the lung. Intravascular cell labeling, cell transplantation, and
fate-mapping studies established that classical CD14+ blood monocytes derived
from HSPCs migrated into lung tissue and gave rise to human interstitial and
alveolar macrophages. In contrast, non-classical CD16+ blood monocytes
preferentially generated macrophages resident in the lung vasculature
(pulmonary intravascular macrophages). Finally, single-cell RNA-sequencing defined
intermediate differentiation stages in human lung macrophage development from
blood monocytes. This study identifies distinct developmental pathways from circulating monocytes to lung macrophages and reveals how cellular
origin contributes to human macrophage identity, diversity, and localization in
vivo.<br>